p53-dependent apoptosis and transcription of p21waf/cip1/sdi1 in SCID mice following gamma-irradiation.
The recruitment and activation of DNA-repair mechanisms at the sites of DNA-damage after exposure of cells to genotoxic stress are poorly understood. The DNA-dependent kinase (DNA-PK) was considered to be a likely candidate for initiating these events because of the conditions required for its activation, its phosphorylation of p53 in vitro and the extreme radiosensitivity induced by its inactivation in vivo. We analyzed irradiation-induced p53-activation in SCID mice, which lack DNA-PK activity, and found that p53-dependent apoptosis and p21waf/cip1/sdi1 transcription in these animals are at least as efficient as in wild-type mice. Thus, our results show that DNA-PK is not the main sensor for genotoxic stress and is not required for p53 activation. In fact, they rather suggest that DNA-PK may play a role in p53 down-regulation.
Candéias
S M
SM
Intramural Research Support Program, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA.
Durum
S K
SK
Muegge
K
K
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics* / Q000502:physiology / Q000528:radiation effects; D004249:DNA Damage; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D004789:Enzyme Activation / Q000528:radiation effects; D005720:Gamma Rays; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016513:Mice, SCID; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology / Q000528:radiation effects; D014158:Transcription, Genetic / Q000528:radiation effects*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000502:physiology* / Q000528:radiation effects
C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D051747:DNA-Activated Protein Kinase; D017346:Protein Serine-Threonine Kinases